Choline and physostigmine enhance haloperidol-induced HVA and DOPAC accumulation

Nigrostriatal neurons respond to dopamine receptor blockade by increasing their firing frequency. We observe that the concurrent administration to rats of cholinergic agonists and haloperidol, a dopamine receptor antagonist, produces a synergistic acceleration in striatal dopamine turnover. Doses of choline and physostigmine which, when given alone, have no effect, enhance the haloperidol-induced accumulation of the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid. These results support the hypothesis that the extent to which nigrostriatal neurons are modulated by cholinergic receptor activation depends on their firing frequency.